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1.
Med Oncol ; 41(11): 249, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316239

RESUMEN

The incidence of lung cancer continues to grow globally, contributing to an ever-increasing load on healthcare systems. Emerging evidence has indicated lowered efficacy of conventional treatment strategies, such as chemotherapy, surgical interventions and radiotherapy, prompting the need for exploring alternative interventions. A growing focus on immunotherapy and the development of personalized medicine has paved the way for vaccine-based delivery in lung cancer. With various prominent targets such as CD8+T cells and PD-L1, immune-targeted, anti-cancer vaccines have been evaluated in both, pre-clinical and clinical settings, to improve therapeutic outcomes. However, there are a number of challenges that must be addressed, including the scalability of such delivery systems, heterogeneity of lung cancers, and long-term safety as well as efficacy. In addition to this, natural compounds, in combination with immunotherapy, have gained considerable research interest in recent times. This makes it necessary to explore their role in synergism with immune-targeted agents. The authors of this review aim to offer an overview of recent advances in our understanding of lung cancer pathogenesis, detection and management strategies, and the emergence of immunotherapy with a special focus on vaccine delivery. This finding is supported with evidence from testing in non-human and human models, showcasing promising results. Prospects for phytotherapy have also been discussed, in order to combat some pitfalls and limitations. Finally, the future perspectives of vaccine usage in lung cancer management have also been discussed, to offer a holistic perspective to readers, and to prompt further research in the domain.


Asunto(s)
Vacunas contra el Cáncer , Inmunoterapia , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Vacunas contra el Cáncer/uso terapéutico , Inmunoterapia/métodos , Animales
2.
Med Oncol ; 41(9): 210, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060753

RESUMEN

According to the World Health Organization, cancer is the foremost cause of mortality globally. Various phytochemicals from natural sources have been extensively studied for their anticancer properties. Allicin, a powerful organosulfur compound derived from garlic, exhibits anticancer, antioxidant, anti-inflammatory, antifungal, and antibacterial properties. This review aims to update and evaluate the chemistry, composition, mechanisms of action, and pharmacokinetics Allicin. Allicin has garnered significant attention for its potential role in modulating Fas-FasL, Bcl2-Bax, PI3K-Akt-mTOR, autophagy, and miRNA pathways. At the molecular level, allicin induces the release of cytochrome c from the mitochondria and enhances the activation of caspases-3, -8, and -9. This is accompanied by the simultaneous upregulation of Bax and Fas expression in tumor cells. Allicin can inhibit excessive autophagy by activating the PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Allicin-loaded nano-formulations efficiently induce apoptosis in cancer cells while minimizing toxicity to normal cells. Safety and clinical aspects are meticulously scrutinized, providing insights into the tolerability and adverse effects associated with allicin administration, along with an overview of current clinical trials evaluating its therapeutic potential. In conclusion, this review underscores the promising prospects of allicin as a dietary-derived medicinal compound for cancer therapy. It emphasizes the need for further research to elucidate its precise mechanisms of action, optimize delivery strategies, and validate its efficacy in clinical settings.


Asunto(s)
Apoptosis , Disulfuros , Neoplasias , Transducción de Señal , Ácidos Sulfínicos , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéutico , Humanos , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico
3.
J Cancer Res Clin Oncol ; 150(7): 370, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066940

RESUMEN

Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.


Asunto(s)
Neoplasias Gastrointestinales , Terpenos , Humanos , Neoplasias Gastrointestinales/prevención & control , Neoplasias Gastrointestinales/tratamiento farmacológico , Terpenos/uso terapéutico , Terpenos/farmacología , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/farmacología
5.
Antioxidants (Basel) ; 13(3)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38539849

RESUMEN

Oxidative burden plays a central role in Alzheimer's disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. However, recent studies have also shown that exosomes are crucial responders to oxidative stress in different tissues. Thus, this offers new insights and mechanistic links within the complex pathogenesis of AD through the involvement of oxidative stress and exosomes. Several studies have indicated that exosomes, acting as intracellular communicators, disseminate oxidatively modified contents from one cell to another, propagating the pathology of AD. Another emerging aspect is the exosome-mediated inhibition of ferroptosis in multiple tissues under different conditions which may have a role in neurodegenerative diseases as well. Apart from their involvement in the pathogenesis of AD, exosomes enter the bloodstream serving as novel noninvasive biomarkers for AD; some of the exosome contents also reflect the cerebral oxidative stress in this disease condition. This review highlights the intricate interplay between oxidative stress and exosome dynamics and underscores the potential of exosomes as a novel tool in AD diagnosis.

6.
Stress Biol ; 4(1): 10, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38311681

RESUMEN

In the ecosphere, plants interact with environmental biotic and abiotic partners, where unbalanced interactions can induce unfavourable stress conditions. Abiotic factors (temperature, water, and salt) are primarily required for plants healthy survival, and any change in their availability is reflected as a stress signal. In certain cases, the presence of infectious pathogens such as viruses, bacteria, fungi, protozoa, nematodes, and insects can also create stress conditions in plants, leading to the emergence of disease or deficiency symptoms. While these symptoms are often typical of abiotic or biotic stress, however, there are instances where they can intensify under specific conditions. Here, we primarily summarize the viral interactions with plants during abiotic stress to understand how these associations are linked together during viral pathogenesis. Secondly, focus is given to the beneficial effects of root-associated symbiotic bacteria in fulfilling the basic needs of plants during normal as well as abiotic stress conditions. The modulations of plant functional proteins, and their occurrence/cross-talk, with pathogen (virus) and symbiont (bacteria) molecules are also discussed. Furthermore, we have highlighted the biochemical and systematic adaptations that develop in plants due to bacterial symbiosis to encounter stress hallmarks. Lastly, directions are provided towards exploring potential rhizospheric bacteria to maintain plant-microbes ecosystem and manage abiotic stress in plants to achieve better trait health in the horticulture crops.

7.
Naunyn Schmiedebergs Arch Pharmacol ; 397(3): 1311-1326, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37695334

RESUMEN

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Polímeros/química , Polímeros/uso terapéutico , Sistemas de Liberación de Medicamentos , Polietilenglicoles/química , Neoplasias/tratamiento farmacológico , Inmunoterapia , Nanopartículas/química , Microambiente Tumoral
8.
Heliyon ; 9(11): e21824, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38034707

RESUMEN

These days carbon dots have been developed for multiple biomedical applications. In the current study, the transfection potential of synthesized carbon dots from single biopolymers such as chitosan, PEI-2kDa, and PEI-25kDa (CS-CDs, PEI2-CDs, and PEI25-CDs) and by combining two biopolymers (CP2-CDs and CP25-CDs) through a bottom-up approach have been investigated. The characterization studies revealed successful synthesis of fluorescent, positively charged carbon dots <20 nm in size. Synthesized carbon dots formed a stable complex with plasmid DNA (EGFP-N1) and miRNA-153 that protected DNA/miRNA from serum-induced degradation. In-vitro cytotoxicity analysis revealed minimal cytotoxicity in cancer cell lines (A549 and MDA-MB-231). In-vitro transfection of EGFP-N1 plasmid DNA with PEI2-CDs, PEI25-CDs and CP25-CDs demonstrated that these CDs could strongly transfect A549 and MDA-MB-231 cells. The highest EGFP-N1 plasmid transfection efficiency was observed with PEI2-CDs at a weight ratio of 32:1. PEI25-CDs polyplex showed maximum transfection at a weight ratio of 8:1 in A549 at a weight ratio of 16:1 in MDA-MB-231 cells. CP25-CDs exhibited the highest transfection at a weight ratio of 16:1 in both cell lines. The in-vitro transfection of target miRNA, i.e., miR-153 in A549 and MDA-MB-231 cells with PEI2-CDs, PEI25-CDs, and CP25-CDs suggested successful transfer of miR-153 into cells which induced significant cell death in both cell lines. Importantly, CS-CDs and CP2-CDs could be tolerated by cells up to 200 µg/mL concentration, while PEI2-CDs, PEI25-CDs, and CP25-CDs showed non-cytotoxic behavior at low concentrations (25 µg/mL). Together, these results suggest that a combination of carbon dots synthesized from chitosan and PEI (CP25-CDs) could be a novel vector for transfection nucleic acids that can be utilized in cancer therapy.

9.
Artículo en Inglés | MEDLINE | ID: mdl-37682510

RESUMEN

In pursuit of a novel effective treatment for prostate cancer, methanolic extract of Stephania glabra tubers (Sg-ME) was utilized to fabricate silver (Sg-AgNP), copper oxide (Sg-CuONP), and silver-copper bimetallic nanoparticles (Sg-BNP). The characterization of the nanoparticles confirmed spherical shape with average diameters of 30.72, 32.19, and 25.59 nm of Sg-AgNP, Sg-CuONP, and Sg-BNP, respectively. Interestingly, these nanoparticles exhibited significant cytotoxicity toward the prostate cancer (PC3) cell line while being non-toxic toward normal cells. The nanoparticles were capable of inducing apoptosis in PC3 cells by enhancing reactive oxygen species (ROS) generation and mitochondrial depolarization. Furthermore, the shrinkage of 3D prostate tumor spheroids was observed after 4 days of treatment with these green nanoparticles. The 3D model system was less susceptible to nanoparticles as compared to the 2D model system. Sg-BNP showed the highest anticancer potential on 2D and 3D prostate cancer models.

10.
Curr Gene Ther ; 23(5): 330-342, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37728084

RESUMEN

The second most pervasive cancer affecting the survival of women across the world is breast cancer. One of the biggest challenges in breast cancer treatment is the chemoresistance of cancer cells to various medications after some time. Therefore, highly specific blood-based biomarkers are required for early breast cancer diagnosis to overcome chemoresistance and improve patient survival. These days, exosomal miRNAs have attracted much attention as early diagnostic blood-based biomarkers because of their high stability, secretion from malignant tumor cells, and excellent specificity for different breast cancer subtypes. In addition, exosomal miRNAs regulate cell proliferation, invasion, metastasis, and apoptosis by binding to the 3'UTR of their target genes and limiting their production. This review focuses on the functions of exosomal miRNAs in tumorigenesis via targeting multiple signaling pathways as well as chemosensitivity and resistance mechanisms. In addition, the growing pieces of evidence discussed in this review suggest that circulating exosomal miRNAs could be utilized as potential next-generation therapeutic target vehicles in the treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , MicroARNs/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Regiones no Traducidas 3' , Apoptosis , Carcinogénesis
11.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3443-3458, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37490121

RESUMEN

One of the well-studied older molecules, quercetin, is found in large quantities in many fruits and vegetables. Natural anti-oxidant quercetin has demonstrated numerous pharmacological properties in preclinical and clinical research, including anti-inflammatory and anti-cancer effects. Due to its ability to control cell signaling pathways, including NF-κB, p53, activated protein-1 (AP-1), STAT3, and epidermal growth response-1 (Egr-1), which is essential in the initiation and proliferation of cancer, it has gained a lot of fame as an anticancer molecule. Recent research suggests that using nanoformulations can help quercetin to overcome its hydrophobicity while also enhancing its stability and cellular bioavailability both in vitro and in vivo. The main aim of this review is to focus on the comprehensive insights of several nanoformulations, including liposomes, nano gels, micelles, solid lipid nanoparticles (SLN), polymer nanoparticles, gold nanoparticles, and cyclodextrin complexes, to transport quercetin for application in cancer.


Asunto(s)
Nanopartículas del Metal , Nanopartículas , Neoplasias , Humanos , Quercetina/farmacología , Oro , Antioxidantes/farmacología , Neoplasias/tratamiento farmacológico
12.
Environ Res ; 233: 116476, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37348632

RESUMEN

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.


Asunto(s)
Curcumina , Neoplasias , Humanos , Curcumina/uso terapéutico , Curcumina/farmacología , Ácido Fólico/uso terapéutico , Neoplasias/tratamiento farmacológico , Solubilidad
13.
Environ Sci Pollut Res Int ; 30(31): 77622-77641, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37258806

RESUMEN

In this work, CQDs decorated MnIn2S4/CdS/Bi2S3 heterojunction was prepared successfully by hydrothermal technique for photocatalytic disinfection of Escherichia coli (E. coli) and mineralization of methyl orange (MO) dye. The charge transferal route and mineralization process in CQDs-MnIn2S4/CdS/Bi2S3 heterojunction were comprehensively investigated by advanced spectroscopic techniques. The improved visible-light activity and enhanced photo-generated charge transferal efficacy caused dual Z-scheme CQDs-MnIn2S4/CdS/Bi2S3 heterojunction to achieve boosted photodegradation ability. The catalytic degradation trend was followed as CQDs-MnIn2S4/CdS/Bi2S3 > MnIn2S4 > CdS > Bi2S3. The dye was mineralized within 180 min under visible light irradiation. The effect of reaction parameters, pH effect, catalyst dosage, and H2O2 addition on MO degradation was also investigated. The degradation rate was maximal at pH 4 with a pseudo-first-order rate constant, 0.0438 min-1. The assessment of antibacterial properties revealed that CQDs-MnIn2S4/CdS/Bi2S3 composite effectively inactivated E. coli under visible light. Scavenging experiments, transient photocurrent response, and electron spin resonance spectroscopy suggested that •[Formula: see text] and holes were the dominant reactive species. The Z-scheme heterojunction is recyclable up to ten photocatalytic cycles according to recycling experiments. This research indicates the importance of dual Z-scheme CQDs decorated MnIn2S4/CdS/Bi2S3 heterojunction in wastewater remediation.


Asunto(s)
Carbono , Puntos Cuánticos , Puntos Cuánticos/química , Escherichia coli , Peróxido de Hidrógeno , Antibacterianos/química , Luz
14.
Indian J Microbiol ; 63(1): 73-83, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37188239

RESUMEN

Bacterial infection is a major crisis of 21st era and the emergence of multidrug resistant (MDR) pathogens cause significant health problems. We developed, green chemistry-based silver nanoparticles (G-Ag NPs) using Citrus pseudolimon fruit peel extract. G-Ag NPs has a spherical shape in the range of ~ 40 nm with a surface charge of - 31 Mv. This nano-bioagent is an eco-friendly tool to combat menace of MDR. Biochemical tests prove that G-Ag NPs are compatible with human red blood cells and peripheral blood mononuclear cells. There have been many reports on the synthesis of silver nanoparticles, but this study suggests a green technique for making non-cytotoxic, non-hemolytic organometallic silver nanoparticles with a high therapeutic index for possible use in the medical field. On the same line, G-Ag NPs are very effective against Mycobacterium sp. and MDR strains including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patient samples. Based on it, we filed a patent to Indian Patent Office (reference no. 202111048797) which can revolutionize the prevention of biomedical device borne infections in hospital pre/post-operated cases. This work could be further explored in future by in vivo experimentation with mice model to direct its possible clinical utility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01061-0.

15.
Biotechnol Adv ; 66: 108149, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37030554

RESUMEN

Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and cell-to-cell interaction. Alterations in the N-linked or O-linked glycosylation pattern of regulatory proteins like transcription factors or cellular receptors lead to many diseases, including cancer. These alterations give rise to micro- and macro-heterogeneity in tumor cells. Here, we review the role of O- and N-linked glycosylation and its regulatory function in autoimmunity and aberrant glycosylation in cancer. The change in cellular glycome could result from a change in the expression of glycosidases or glycosyltransferases like N-acetyl-glucosaminyl transferase V, FUT8, ST6Gal-I, DPAGT1, etc., impact the glycosylation of target proteins leading to transformation. Moreover, the mutations in glycogenes affect glycosylation patterns on immune cells leading to other related manifestations like pro- or anti-inflammatory effects. In recent years, understanding the glycome to cancer indicates that it can be utilized for both diagnosis/prognosis as well as immunotherapy. Studies involving mass spectrometry of proteome, site- and structure-specific glycoproteomics, or transcriptomics/genomics of patient samples and cancer models revealed the importance of glycosylation homeostasis in cancer biology. The development of emerging technologies, such as the lectin microarray, has facilitated research on the structure and function of glycans and glycosylation. Newly developed devices allow for high-throughput, high-speed, and precise research on aberrant glycosylation. This paper also discusses emerging technologies and clinical applications of glycosylation.


Asunto(s)
Neoplasias , Humanos , Glicosilación , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Glicosiltransferasas/metabolismo , Lectinas/metabolismo , Inmunoterapia , Polisacáridos/química
16.
Biotechnol Genet Eng Rev ; : 1-34, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36809927

RESUMEN

High demand of bioactive molecules (food additives, antibiotics, plant growth enhancers, cosmetics, pigments and other commercial products) is the prime need for the betterment of human life where the applicability of the synthetic chemical product is on the saturation due to associated toxicity and ornamentations. It has been noticed that the discovery and productivity of such molecules in natural scenarios are limited due to low cellular yields as well as less optimized conventional methods. In this respect, microbial cell factories timely fulfilling the requirement of synthesizing bioactive molecules by improving production yield and screening more promising structural homologues of the native molecule. Where the robustness of the microbial host can be potentially achieved by taking advantage of cell engineering approaches such as tuning functional and adjustable factors, metabolic balancing, adapting cellular transcription machinery, applying high throughput OMICs tools, stability of genotype/phenotype, organelle optimizations, genome editing (CRISPER/Cas mediated system) and also by developing accurate model systems via machine-learning tools. In this article, we provide an overview from traditional to recent trends and the application of newly developed technologies, for strengthening the systemic approaches and providing future directions for enhancing the robustness of microbial cell factories to speed up the production of biomolecules for commercial purposes.

17.
Pharmacol Rep ; 75(2): 482-489, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36849757

RESUMEN

BACKGROUND: Inhibitors of glucose transporters are being explored as potential anti-cancer drugs. Decreased cerebral glucose utilization with reduced levels of several glucose transporters is also an important pathogenic signature of neurodegeneration of Alzheimer's disease, but its exact role in the pathogenesis of this disease is not established. We explored in an experimental model if inhibitors of glucose transporters could lead to altered amyloid-beta homeostasis, mitochondrial dysfunction, and neuronal death, which are relevant in the pathogenesis of Alzheimer's disease. METHODS: SH-SY5Y cells (human neuroblastoma cell line) were exposed to an inhibitor (WZB117) of several types of glucose transporters. We examined the effects of glucose hypometabolism on SH-SY5Y cells in terms of mitochondrial functions, production of reactive oxygen species, amyloid-beta homeostasis, and neural cell death. The effect of ß-hydroxybutyrate in ameliorating the effects of WZB117 on SH-SY5Y cells was also examined. RESULTS: We observed that exposure of SH-SY5Y cells to WZB117 caused mitochondrial dysfunction, increased production of reactive oxygen species, loss of cell viability, increased expression of BACE 1, and intracellular accumulation of amyloid ß peptide (Aß42). All the effects of WZB117 could be markedly prevented by co-treatment with ß-hydroxybutyrate. Cyclosporine A, a blocker of mitochondrial permeability transition pore (mPTP) activation, could not prevent cell death caused by WZB117. CONCLUSION: Results in this neuroblastoma model have implications for the pathogenesis of Alzheimer's disease and warrant further explorations of WZB117 in primary cultures of neurons and experimental animal models.


Asunto(s)
Enfermedad de Alzheimer , Neuroblastoma , Animales , Humanos , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Ácido 3-Hidroxibutírico/farmacología , Ácido 3-Hidroxibutírico/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Glucosa , Línea Celular Tumoral , Fragmentos de Péptidos/metabolismo
18.
Naunyn Schmiedebergs Arch Pharmacol ; 396(2): 191-212, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36214865

RESUMEN

Oroxylin A (OA), a well-known constituent of the root of Scutellariae plants, has been used in ethnomedicine already for centuries in treating various neoplastic disorders. However, only recent molecular studies have revealed the different mechanisms behind its action, demonstrating antiproliferative, anti-inflammatory, and proapoptotic effects, restricting also the spread of cancer cells to distant organs. A variety of cellular targets and modulated signal transduction pathways regulated by OA have been determined in diverse cells derived from different malignant tissues. In this review article, these anticancer activities are thoroughly described, representing OA as a potential lead structure for the design of novel more potent anticancer medicines. In addition, co-effects of this natural compound with conventional anticancer agents are analyzed and the advantages provided by nanotechnological methods for more efficient application of OA are discussed. In this way, OA might represent an excellent example of using ethnopharmacological knowledge for designing modern medicines.


Asunto(s)
Antineoplásicos , Flavonoides , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal , Línea Celular Tumoral
19.
Hum Cell ; 36(1): 98-120, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36334180

RESUMEN

Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8+ T cells, natural killer (NK) cells, tumor associated macrophages (TAMs) and stromal cells. The myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs), are also key tumor-promoting immune cells. These potent immunosuppressive networks avert tumor rejection at various stages, affecting immunotherapies' outcomes. Numerous clinical trials have elucidated that disruption of immunosuppression could be achieved via checkpoint inhibitors. Another approach utilizes enzymes that can restore the body's potential to counter cancer by triggering the immune system inhibited by the tumor microenvironment. These immunotherapeutic enzymes can catalyze an immunostimulatory signal and modulate the tumor microenvironment via effector molecules. Herein, we have discussed the immuno-metabolic roles of various enzymes like ATP-dephosphorylating ectoenzymes, inducible Nitric Oxide Synthase, phenylamine, tryptophan, and arginine catabolizing enzymes in cancer immunotherapy. Understanding the detailed molecular mechanisms of the enzymes involved in modulating the tumor microenvironment may help find new opportunities for cancer therapeutics.


Asunto(s)
Células Supresoras de Origen Mieloide , Neoplasias , Humanos , Linfocitos T CD8-positivos , Inmunoterapia , Neoplasias/terapia , Tolerancia Inmunológica , Microambiente Tumoral
20.
Mol Biol Rep ; 50(3): 2685-2700, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36534236

RESUMEN

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1 , Inmunoterapia/métodos
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